Descrizione del progetto
Meccanismi neuronali alla base dell’attenuazione della memoria traumatica
Paura, rabbia, ansia e depressione o senso di colpa sono tutte reazioni comuni al trauma. Il ricordo angosciante di un evento traumatico può tuttavia essere attenuato nel tempo e attraverso un processo psicologico di adattamento. Spesso, però, la mancanza di supporto terapeutico porta a gravi disturbi legati al trauma. In questo contesto, il progetto EthoFearless, finanziato dal Consiglio europeo della ricerca, studierà (per la prima volta) i circuiti neurali alla base dell’estinzione dei ricordi traumatici indotti dall’esposizione a minacce naturalistiche, ossia predatori e conspecifici aggressivi. I risultati apriranno la strada all’individuazione di nuovi bersagli terapeutici per i disturbi legati al trauma e faranno luce sul modo in cui il cervello può aggiornare in modo flessibile i ricordi complessi.
Obiettivo
Traumatic experiences generate among the strongest memories that can result in trauma-related disorders. Despite the high prevalence of these disorders, effective treatment options are scarce, calling for a deterministic understanding of the neuronal mechanisms underlying traumatic memory attenuation. For this, rodent studies classically use fear extinction paradigms where aversive experiences are modeled with the exposure to an electrical foot shock. However, the simple nature of this stimulus does not mirror the complexity of traumatic events in humans which is likely to be processed by equally complex networks. Here, I propose to investigate for the first time the neural circuits underlying the extinction of traumatic memories induced by exposure to naturalistic threats, namely, predators and aggressive conspecifics. First, we will compile a comprehensive atlas of brain activity underlying extinction of these ethological traumas and generate network organization models, which will be causally probed by pathway-specific chemogenetic manipulations. Second, we will characterize the functional input-output connectome of ethological extinction centers using a combination of viral tracing, neuronal activity and optogenetically assisted circuit mapping. This set of data will, third, provide the substrate for the study of the neurophysiological and molecular mechanisms underlying efficient extinction of ethological traumas, which will be analyzed by pathway-specific in-vivo Ca2+ imaging, closed-loop optogenetics, ex-vivo electrophysiology and RNA sequencing. Lastly, we will investigate whether impairments at the level of these newly identified networks underlie extinction deficits at the basis of trauma-related disorders. Together, these results will pave the way for the identification of novel therapeutical targets for trauma-related disorders and shed light on how the brain can flexibly update complex memories.
Campo scientifico
Parole chiave
Programma(i)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Argomento(i)
Meccanismo di finanziamento
HORIZON-ERC - HORIZON ERC GrantsIstituzione ospitante
75794 Paris
Francia